A Laboratory Phenotype/Genotype Correlation of 1167 French Patients From 670 Families With von Willebrand Disease: A New Epidemiologic Picture
von Willebrand disease (VWD) is a genetic bleeding disease due to a defect of von Willebrand factor (VWF), a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels
Gespeichert in:
| Veröffentlicht in: | Medicine (Baltimore) 2016-03, Vol.95 (11), p.e3038-e3038 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e3038 |
|---|---|
| container_issue | 11 |
| container_start_page | e3038 |
| container_title | Medicine (Baltimore) |
| container_volume | 95 |
| creator | Veyradier, Agnès Boisseau, Pierre Fressinaud, Edith Caron, Claudine Ternisien, Catherine Giraud, Mathilde Zawadzki, Christophe Trossaert, Marc Itzhar-Baïkian, Nathalie Dreyfus, Marie d'Oiron, Roseline Borel-Derlon, Annie Susen, Sophie Bezieau, Stéphane Denis, Cécile V Goudemand, Jenny |
| description | von Willebrand disease (VWD) is a genetic bleeding disease due to a defect of von Willebrand factor (VWF), a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels |
| doi_str_mv | 10.1097/MD.0000000000003038 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4839904</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1774530124</sourcerecordid><originalsourceid>FETCH-LOGICAL-c225t-318bb076b049dc3f6be628a40da7613842d89845b5baa37b5d9091044b4ec4cc3</originalsourceid><addsrcrecordid>eNpdUU1vEzEQtRCIpoVfgIR85LKtv9Zec0CKkqZFSiGHVj1atnfSGHnXwd4U5U_wm7tV06owl_l8b2b0EPpEySklWp1dzU_JK-OEN2_QhNZcVrWW4i2aEMLqSmkljtBxKb8IoVwx8R4dMakbSRmfoL9TvLQuZTukvMerDfRp2G_h7OIQ4FnKGaIdQupxWmNKpcKLDL3f4NVYhX4oY546LBXBC9uFGKDg2zBs8P0IuQ0xgsu2b_E8FLAFvuIp_gF_8Pk2tNCFFNNd8HgV_LDL8AG9W9tY4OPBn6Cbxfn17LJa_rz4PpsuK89YPVScNs4RJR0RuvV8LR1I1lhBWqsk5Y1gbaMbUbvaWcuVq1tNNCVCOAFeeM9P0Lcn3u3OddD68Y1so9nm0Nm8N8kG82-nDxtzl-6NaLjWRIwEXw4EOf3eQRlMF4qHGG0PaVcMVUrUnFD2OMqfRn1OpWRYv6yhxDwqaa7m5n8lR9Tn1xe-YJ6l4w8zAJoV</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1774530124</pqid></control><display><type>article</type><title>A Laboratory Phenotype/Genotype Correlation of 1167 French Patients From 670 Families With von Willebrand Disease: A New Epidemiologic Picture</title><source>Wolters Kluwer Open Health</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>IngentaConnect Free/Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Veyradier, Agnès ; Boisseau, Pierre ; Fressinaud, Edith ; Caron, Claudine ; Ternisien, Catherine ; Giraud, Mathilde ; Zawadzki, Christophe ; Trossaert, Marc ; Itzhar-Baïkian, Nathalie ; Dreyfus, Marie ; d'Oiron, Roseline ; Borel-Derlon, Annie ; Susen, Sophie ; Bezieau, Stéphane ; Denis, Cécile V ; Goudemand, Jenny</creator><creatorcontrib>Veyradier, Agnès ; Boisseau, Pierre ; Fressinaud, Edith ; Caron, Claudine ; Ternisien, Catherine ; Giraud, Mathilde ; Zawadzki, Christophe ; Trossaert, Marc ; Itzhar-Baïkian, Nathalie ; Dreyfus, Marie ; d'Oiron, Roseline ; Borel-Derlon, Annie ; Susen, Sophie ; Bezieau, Stéphane ; Denis, Cécile V ; Goudemand, Jenny ; French Reference Center for von Willebrand disease</creatorcontrib><description>von Willebrand disease (VWD) is a genetic bleeding disease due to a defect of von Willebrand factor (VWF), a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels <50 IU/dL) or virtually total (type 3 with undetectable VWF levels) and also qualitative defects of VWF (type 2 variants with discrepant antigenic and functional VWF levels). The most bleeding forms of VWD usually do not concern type 1 patients with the mildest VWF defects (VWF levels between 30 and 50 IU/dL). The French reference center for VWD performed a laboratory phenotypic and genotypic analysis in 1167 VWD patients (670 families) selected by their basic biologic phenotype: type 3, type 2, and type 1 with VWF levels <30 IU/dL. In these patients indeed, to achieve an accurate diagnosis of VWD type and subtype is crucial for the management (treatment and genetic counseling). A phenotype/genotype correlation was present in 99.3% of cases; 323 distinct VWF sequence variations (58% of novel) were identified (missense 67% versus truncating 33%). The distribution of VWD types was: 25% of type 1, 8% of type 3, 66% of type 2 (2A: 18%, 2B: 17%, 2M: 19%, 2N: 12%), and 1% of undetermined type. Type 1 VWD was related either to a defective synthesis/secretion or to an accelerated clearance of VWF. In type 3 VWD, bi-allelic mutations of VWF were found in almost all patients. In type 2A, the most frequent mechanism was a hyper-proteolysis of VWF. Type 2B showed 85% of patients with deleterious mutations (distinct from type 2B New York). Type 2M was linked to a defective binding of VWF to platelet glycoprotein Ib or to collagen. Type 2N VWD included almost half type 2N/3. This biologic study emphasizes the complex mechanisms for both quantitative and qualitative VWF defects in VWD. In addition, this study provides a new epidemiologic picture of the most bleeding forms of VWD in which qualitative defects are predominant.</description><identifier>ISSN: 0025-7974</identifier><identifier>EISSN: 1536-5964</identifier><identifier>DOI: 10.1097/MD.0000000000003038</identifier><identifier>PMID: 26986123</identifier><language>eng</language><publisher>United States: Wolters Kluwer Health</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; France - epidemiology ; Genotype ; Humans ; Infant ; Male ; Middle Aged ; Mutation ; Observational Study ; Phenotype ; von Willebrand Diseases - epidemiology ; von Willebrand Diseases - genetics ; Young Adult</subject><ispartof>Medicine (Baltimore), 2016-03, Vol.95 (11), p.e3038-e3038</ispartof><rights>Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c225t-318bb076b049dc3f6be628a40da7613842d89845b5baa37b5d9091044b4ec4cc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839904/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839904/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26986123$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Veyradier, Agnès</creatorcontrib><creatorcontrib>Boisseau, Pierre</creatorcontrib><creatorcontrib>Fressinaud, Edith</creatorcontrib><creatorcontrib>Caron, Claudine</creatorcontrib><creatorcontrib>Ternisien, Catherine</creatorcontrib><creatorcontrib>Giraud, Mathilde</creatorcontrib><creatorcontrib>Zawadzki, Christophe</creatorcontrib><creatorcontrib>Trossaert, Marc</creatorcontrib><creatorcontrib>Itzhar-Baïkian, Nathalie</creatorcontrib><creatorcontrib>Dreyfus, Marie</creatorcontrib><creatorcontrib>d'Oiron, Roseline</creatorcontrib><creatorcontrib>Borel-Derlon, Annie</creatorcontrib><creatorcontrib>Susen, Sophie</creatorcontrib><creatorcontrib>Bezieau, Stéphane</creatorcontrib><creatorcontrib>Denis, Cécile V</creatorcontrib><creatorcontrib>Goudemand, Jenny</creatorcontrib><creatorcontrib>French Reference Center for von Willebrand disease</creatorcontrib><title>A Laboratory Phenotype/Genotype Correlation of 1167 French Patients From 670 Families With von Willebrand Disease: A New Epidemiologic Picture</title><title>Medicine (Baltimore)</title><addtitle>Medicine (Baltimore)</addtitle><description>von Willebrand disease (VWD) is a genetic bleeding disease due to a defect of von Willebrand factor (VWF), a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels <50 IU/dL) or virtually total (type 3 with undetectable VWF levels) and also qualitative defects of VWF (type 2 variants with discrepant antigenic and functional VWF levels). The most bleeding forms of VWD usually do not concern type 1 patients with the mildest VWF defects (VWF levels between 30 and 50 IU/dL). The French reference center for VWD performed a laboratory phenotypic and genotypic analysis in 1167 VWD patients (670 families) selected by their basic biologic phenotype: type 3, type 2, and type 1 with VWF levels <30 IU/dL. In these patients indeed, to achieve an accurate diagnosis of VWD type and subtype is crucial for the management (treatment and genetic counseling). A phenotype/genotype correlation was present in 99.3% of cases; 323 distinct VWF sequence variations (58% of novel) were identified (missense 67% versus truncating 33%). The distribution of VWD types was: 25% of type 1, 8% of type 3, 66% of type 2 (2A: 18%, 2B: 17%, 2M: 19%, 2N: 12%), and 1% of undetermined type. Type 1 VWD was related either to a defective synthesis/secretion or to an accelerated clearance of VWF. In type 3 VWD, bi-allelic mutations of VWF were found in almost all patients. In type 2A, the most frequent mechanism was a hyper-proteolysis of VWF. Type 2B showed 85% of patients with deleterious mutations (distinct from type 2B New York). Type 2M was linked to a defective binding of VWF to platelet glycoprotein Ib or to collagen. Type 2N VWD included almost half type 2N/3. This biologic study emphasizes the complex mechanisms for both quantitative and qualitative VWF defects in VWD. In addition, this study provides a new epidemiologic picture of the most bleeding forms of VWD in which qualitative defects are predominant.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Female</subject><subject>France - epidemiology</subject><subject>Genotype</subject><subject>Humans</subject><subject>Infant</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Observational Study</subject><subject>Phenotype</subject><subject>von Willebrand Diseases - epidemiology</subject><subject>von Willebrand Diseases - genetics</subject><subject>Young Adult</subject><issn>0025-7974</issn><issn>1536-5964</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUU1vEzEQtRCIpoVfgIR85LKtv9Zec0CKkqZFSiGHVj1atnfSGHnXwd4U5U_wm7tV06owl_l8b2b0EPpEySklWp1dzU_JK-OEN2_QhNZcVrWW4i2aEMLqSmkljtBxKb8IoVwx8R4dMakbSRmfoL9TvLQuZTukvMerDfRp2G_h7OIQ4FnKGaIdQupxWmNKpcKLDL3f4NVYhX4oY546LBXBC9uFGKDg2zBs8P0IuQ0xgsu2b_E8FLAFvuIp_gF_8Pk2tNCFFNNd8HgV_LDL8AG9W9tY4OPBn6Cbxfn17LJa_rz4PpsuK89YPVScNs4RJR0RuvV8LR1I1lhBWqsk5Y1gbaMbUbvaWcuVq1tNNCVCOAFeeM9P0Lcn3u3OddD68Y1so9nm0Nm8N8kG82-nDxtzl-6NaLjWRIwEXw4EOf3eQRlMF4qHGG0PaVcMVUrUnFD2OMqfRn1OpWRYv6yhxDwqaa7m5n8lR9Tn1xe-YJ6l4w8zAJoV</recordid><startdate>201603</startdate><enddate>201603</enddate><creator>Veyradier, Agnès</creator><creator>Boisseau, Pierre</creator><creator>Fressinaud, Edith</creator><creator>Caron, Claudine</creator><creator>Ternisien, Catherine</creator><creator>Giraud, Mathilde</creator><creator>Zawadzki, Christophe</creator><creator>Trossaert, Marc</creator><creator>Itzhar-Baïkian, Nathalie</creator><creator>Dreyfus, Marie</creator><creator>d'Oiron, Roseline</creator><creator>Borel-Derlon, Annie</creator><creator>Susen, Sophie</creator><creator>Bezieau, Stéphane</creator><creator>Denis, Cécile V</creator><creator>Goudemand, Jenny</creator><general>Wolters Kluwer Health</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201603</creationdate><title>A Laboratory Phenotype/Genotype Correlation of 1167 French Patients From 670 Families With von Willebrand Disease: A New Epidemiologic Picture</title><author>Veyradier, Agnès ; Boisseau, Pierre ; Fressinaud, Edith ; Caron, Claudine ; Ternisien, Catherine ; Giraud, Mathilde ; Zawadzki, Christophe ; Trossaert, Marc ; Itzhar-Baïkian, Nathalie ; Dreyfus, Marie ; d'Oiron, Roseline ; Borel-Derlon, Annie ; Susen, Sophie ; Bezieau, Stéphane ; Denis, Cécile V ; Goudemand, Jenny</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c225t-318bb076b049dc3f6be628a40da7613842d89845b5baa37b5d9091044b4ec4cc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Female</topic><topic>France - epidemiology</topic><topic>Genotype</topic><topic>Humans</topic><topic>Infant</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Observational Study</topic><topic>Phenotype</topic><topic>von Willebrand Diseases - epidemiology</topic><topic>von Willebrand Diseases - genetics</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Veyradier, Agnès</creatorcontrib><creatorcontrib>Boisseau, Pierre</creatorcontrib><creatorcontrib>Fressinaud, Edith</creatorcontrib><creatorcontrib>Caron, Claudine</creatorcontrib><creatorcontrib>Ternisien, Catherine</creatorcontrib><creatorcontrib>Giraud, Mathilde</creatorcontrib><creatorcontrib>Zawadzki, Christophe</creatorcontrib><creatorcontrib>Trossaert, Marc</creatorcontrib><creatorcontrib>Itzhar-Baïkian, Nathalie</creatorcontrib><creatorcontrib>Dreyfus, Marie</creatorcontrib><creatorcontrib>d'Oiron, Roseline</creatorcontrib><creatorcontrib>Borel-Derlon, Annie</creatorcontrib><creatorcontrib>Susen, Sophie</creatorcontrib><creatorcontrib>Bezieau, Stéphane</creatorcontrib><creatorcontrib>Denis, Cécile V</creatorcontrib><creatorcontrib>Goudemand, Jenny</creatorcontrib><creatorcontrib>French Reference Center for von Willebrand disease</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Medicine (Baltimore)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Veyradier, Agnès</au><au>Boisseau, Pierre</au><au>Fressinaud, Edith</au><au>Caron, Claudine</au><au>Ternisien, Catherine</au><au>Giraud, Mathilde</au><au>Zawadzki, Christophe</au><au>Trossaert, Marc</au><au>Itzhar-Baïkian, Nathalie</au><au>Dreyfus, Marie</au><au>d'Oiron, Roseline</au><au>Borel-Derlon, Annie</au><au>Susen, Sophie</au><au>Bezieau, Stéphane</au><au>Denis, Cécile V</au><au>Goudemand, Jenny</au><aucorp>French Reference Center for von Willebrand disease</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Laboratory Phenotype/Genotype Correlation of 1167 French Patients From 670 Families With von Willebrand Disease: A New Epidemiologic Picture</atitle><jtitle>Medicine (Baltimore)</jtitle><addtitle>Medicine (Baltimore)</addtitle><date>2016-03</date><risdate>2016</risdate><volume>95</volume><issue>11</issue><spage>e3038</spage><epage>e3038</epage><pages>e3038-e3038</pages><issn>0025-7974</issn><eissn>1536-5964</eissn><abstract>von Willebrand disease (VWD) is a genetic bleeding disease due to a defect of von Willebrand factor (VWF), a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels <50 IU/dL) or virtually total (type 3 with undetectable VWF levels) and also qualitative defects of VWF (type 2 variants with discrepant antigenic and functional VWF levels). The most bleeding forms of VWD usually do not concern type 1 patients with the mildest VWF defects (VWF levels between 30 and 50 IU/dL). The French reference center for VWD performed a laboratory phenotypic and genotypic analysis in 1167 VWD patients (670 families) selected by their basic biologic phenotype: type 3, type 2, and type 1 with VWF levels <30 IU/dL. In these patients indeed, to achieve an accurate diagnosis of VWD type and subtype is crucial for the management (treatment and genetic counseling). A phenotype/genotype correlation was present in 99.3% of cases; 323 distinct VWF sequence variations (58% of novel) were identified (missense 67% versus truncating 33%). The distribution of VWD types was: 25% of type 1, 8% of type 3, 66% of type 2 (2A: 18%, 2B: 17%, 2M: 19%, 2N: 12%), and 1% of undetermined type. Type 1 VWD was related either to a defective synthesis/secretion or to an accelerated clearance of VWF. In type 3 VWD, bi-allelic mutations of VWF were found in almost all patients. In type 2A, the most frequent mechanism was a hyper-proteolysis of VWF. Type 2B showed 85% of patients with deleterious mutations (distinct from type 2B New York). Type 2M was linked to a defective binding of VWF to platelet glycoprotein Ib or to collagen. Type 2N VWD included almost half type 2N/3. This biologic study emphasizes the complex mechanisms for both quantitative and qualitative VWF defects in VWD. In addition, this study provides a new epidemiologic picture of the most bleeding forms of VWD in which qualitative defects are predominant.</abstract><cop>United States</cop><pub>Wolters Kluwer Health</pub><pmid>26986123</pmid><doi>10.1097/MD.0000000000003038</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0025-7974 |
| ispartof | Medicine (Baltimore), 2016-03, Vol.95 (11), p.e3038-e3038 |
| issn | 0025-7974 1536-5964 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4839904 |
| source | Wolters Kluwer Open Health; MEDLINE; DOAJ Directory of Open Access Journals; IngentaConnect Free/Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Adolescent Adult Aged Aged, 80 and over Child Child, Preschool Female France - epidemiology Genotype Humans Infant Male Middle Aged Mutation Observational Study Phenotype von Willebrand Diseases - epidemiology von Willebrand Diseases - genetics Young Adult |
| title | A Laboratory Phenotype/Genotype Correlation of 1167 French Patients From 670 Families With von Willebrand Disease: A New Epidemiologic Picture |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T20%3A38%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Laboratory%20Phenotype/Genotype%20Correlation%20of%201167%20French%20Patients%20From%20670%20Families%20With%20von%20Willebrand%20Disease:%20A%20New%20Epidemiologic%20Picture&rft.jtitle=Medicine%20(Baltimore)&rft.au=Veyradier,%20Agn%C3%A8s&rft.aucorp=French%20Reference%20Center%20for%20von%20Willebrand%20disease&rft.date=2016-03&rft.volume=95&rft.issue=11&rft.spage=e3038&rft.epage=e3038&rft.pages=e3038-e3038&rft.issn=0025-7974&rft.eissn=1536-5964&rft_id=info:doi/10.1097/MD.0000000000003038&rft_dat=%3Cproquest_pubme%3E1774530124%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1774530124&rft_id=info:pmid/26986123&rfr_iscdi=true |